The herb milk thistle has been used for millennia as part of traditional European remedies for gastrointestinal and liver illness. This herb contains many compounds, some of which are being studied in lab experiments with cells. In these experiments, extracts of milk thistle appear to have anti-inflammatory, anti-cancer and antioxidant activity. What's more, some of the extracts have antiviral activity against hepatitis C virus (HCV). All of these properties have stimulated further interest and research in this herb.

Researchers in Vienna, Austria, have been conducting small clinical trials with an intravenous formulation of a milk thistle extract -- silibinin -- in people with hepatitis C who are unresponsive to standard therapy. Their results are somewhat surprising and suggest that silibinin has potent anti-HCV activity in some people. Much work remains to be done to confirm and extend these findings.

Study Details

For the study, 36 volunteers (5 female, 31 male) were recruited. All had HCV mono-infection and previous standard HCV therapy -- the immune booster interferon and the antiviral drug ribavirin -- had failed to cure them. Their average age was 50 years and most had the hard-to-treat strain of HCV called genotype 1. About 55% had moderate-to-severe liver damage.

The study team first gave participants different intravenous doses of highly purified silibinin, sold as Legalon Sil (made by Madaus GmbH, in Köln, Germany), for one or two weeks, followed by a combination of interferon and ribavirin. Additionally, once participants stopped receiving IV silibinin, they were switched to an oral formulation of a mix of concentrated milk thistle extracts called silymarin. This oral formulation was taken three times daily. So far, most participants have taken silymarin and interferon-ribavirin for at least 24 weeks and the trial will continue for an additional 24 weeks.

Results

High doses -- 15 or 20 mg/kg/day -- of IV silibinin alone caused a significant decline (between 100- and 10,000-fold) in HCV levels. The addition of interferon-ribavirin resulted in a further decline in virus levels.

In two of five participants who received 15 mg/kg/day of IV silibinin, HCV levels fell below the threshold of detection; the lower limit of quantification of the test was 15 international units (IU). Five of nine participants who received the 20 mg/kg/day dose also had HCV levels fall below the 15 IU level.

After 12 weeks of combination therapy, a total of eight participants continued to have very low levels of HCV (less than 15 IU).

Safety

In general, IV silibinin use was well tolerated. Eight participants complained of the following symptoms (some participants had more than one symptom), each of which they described as "mild":

abdominal pain (five people)

diarrhea (two people)

nausea (one person)

headache (two people)

joint pain (one person)

All participants receiving high doses of IV silibinin reported feeling warmer when the herb was infused into their veins; this feeling subsided after 30 minutes.

Intravenous vs. Oral

In this study, IV silibinin appears to have potent anti-HCV activity. However, according to the study team, oral doses of milk thistle extract did not share this effect. The study team suspects that this is likely due to the extensive processing and breakdown of the extracts in the intestine and liver. Previous studies have found that oral formulations of milk thistle result in very low levels of active extracts in the blood. These levels are much lower than seen in lab experiments with liver cells. Taking this into account, it is perhaps not surprising that another study has found that oral milk thistle had no effect on HCV levels in people. Future research will likely use highly purified milk thistle extracts given intravenously.

The current protocol used in the Vienna study is a bit cumbersome -- intravenous infusion over a period of four hours each day. However, the Austrian research team is exploring different schedules, such as five consecutive days weekly and perhaps repeated and longer use of IV silibinin, in people who show a partial response to therapy. Further studies are needed to determine the best dose of silibinin and possible interactions with other drugs. Researchers in Austria and the United States hope to conduct a larger study of IV silibinin followed by interferon-ribavirin treatment in volunteers whose HCV infection was not cleared when previously treated with standard therapy.

Notes on Extracts

Silymarin is the name given to a mix of compounds called flavonoids found in milk thistle. The chief compound in silymarin is silibinin (found as an equal mixture of silibinin A and silibinin). Other compounds found in silymarin include the following:

silydianin

silycristin

isosilybin A

isosylibin B

isosilycrystin

taxifolin

It is likely that other research teams will explore the activity of these compounds for a wide range of conditions.

Acknowledgement

We thank Professor Peter Ferenci, MD, from the Medical University of Vienna for his helpful comments and review.

This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News.
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